Disclosed herein are programmable
bacteria for tumor-targeted immunotherapeutic delivery. In certain embodiments, the programmable
bacteria comprise at least one synchronized
lysis circuit contained in a single
operon which are capable of being further engineered to cyclically produce anti-
cancer therapeutic agents including but not limited to nanobodies against
immune checkpoint inhibitors and over-expressed markers in cancers, toxins, tumor antigens, cytokines, and chemokines. In some embodiments, the programmable
bacteria comprise at least one synchronized
lysis circuit contained in a single
operon and at least one
plasmid producing a therapeutic agent, i.e., at least one
plasmid comprising a
nucleic acid sequence which encodes a therapeutic agent. The disclosure also provides methods of curing and treating
cancer using the programmable bacteria.